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Review
. 2021 Jul 5:12:656455.
doi: 10.3389/fphys.2021.656455. eCollection 2021.

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity

Zhihai Huang  1 , Yulan Zhang  1 , Ruixue Zhou  1 , Luodan Yang  1 , Hongying Pan  1
Affiliations
Review

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity

Zhihai Huang et al. Front Physiol. .

Abstract

The accumulated evidence from animal and human studies supports that exercise is beneficial to physical health. Exercise can upregulate various neurotrophic factors, activate neuroplasticity, and play a positive role in improving and enhancing cerebrovascular function. Due to its economy, convenience, and ability to prevent or ameliorate various aging-related diseases, exercise, a healthy lifestyle, is increasingly popularized by people. However, the mechanism by which exercise performs this function and how it is transmitted from muscles to the brain remains incompletely understood. Here, we review the beneficial effects of exercise with different intensities on the brain with a focus on the positive effects of lactate on neuroplasticity and cerebrovascular plasticity. Based on these recent studies, we propose that lactate, a waste previously misunderstood as a by-product of glycolysis in the past, may be a key signal molecule that regulates the beneficial adaptation of the brain caused by exercise. Importantly, we speculate that a central protective mechanism may underlie the cognitive benefits induced by exercise.

Keywords: brain; cerebrovascular function; lactate; neuroplasticity; physical exercise.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The possible mechanisms of lactate in exercise-induced positive effects on neuroplasticity and cerebrovascular plasticity. Exercise causes muscles to produce lactate, which is then released into the blood and passes through the BBB through different MCTs into the brain parenchyma. Meanwhile, astrocytes may also release lactate during exercise to supply the neural network in response to activated neurons. At the BBB of the microvasculature, lactate binds to HCAR1 to activate it and induces increased VEGF-A expression in the hippocampal dentate gyrus (DG), angiogenesis, and neurogenesis of SVZ through an unidentified pathway. In hippocampal neurons, lactate is transported across the membrane by MCT, activating the SIRT1/PGC1-α/FNDC5/BDNF pathway through an unknown pathway, thereby improving neural plasticity.
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